Conversion of a tyrosine kinase protein substrate to a high affinity ligand by ATP linkage

J Am Chem Soc. 2003 Dec 31;125(52):16172-3. doi: 10.1021/ja0380401.

Abstract

Protein kinases often show low affinity for their protein substrates, which makes it difficult to study kinase-substrate interactions. Here, we show using expressed protein ligation with the signaling protein Src that it is feasible to install a covalently linked ATP moiety into the tail of Src, generating a semisynthetic protein with a high affinity for its cognate tyrosine kinase, Csk. It is also established that this Src-ATP conjugate can be used to selectively pull down Csk from a complex protein mixture. This work outlines a general strategy for identifying an unknown kinase that is responsible for the phosphorylation of a protein substrate on a site of interest.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / analogs & derivatives*
  • Adenosine Triphosphate / chemistry*
  • Adenosine Triphosphate / metabolism
  • Animals
  • CSK Tyrosine-Protein Kinase
  • Kinetics
  • Mice
  • NIH 3T3 Cells
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / chemistry*
  • Protein-Tyrosine Kinases / metabolism
  • src Homology Domains
  • src-Family Kinases

Substances

  • adenosine 5'-O-(3-thiotriphosphate)
  • Adenosine Triphosphate
  • Protein-Tyrosine Kinases
  • CSK Tyrosine-Protein Kinase
  • src-Family Kinases